Exploring the Impact of Hand Dominance on Laparoscopic Surgical Skills Development Using Network Models.

BACKGROUND: Laparoscopic surgery demands high precision and skill, necessitating effective training protocols that account for factors such as hand dominance. This study investigates the impact of hand dominance on the acquisition and proficiency of laparoscopic surgical skills, utilizing a novel assessment method that combines Network Models and electromyography (EMG) data. METHODS: Eighteen participants, comprising both medical and non-medical students, engaged in laparoscopic simulation tasks, including peg transfer and wire loop tasks. Performance was assessed using Network Models to analyze EMG data, capturing muscle activity and learning progression. The NASA Task Load Index (TLX) was employed to evaluate subjective task demands and workload perceptions. RESULTS: Our analysis revealed significant differences in learning progression and skill proficiency between dominant and non-dominant hands, suggesting the need for tailored training approaches. Network Models effectively identified patterns of skill acquisition, while NASA-TLX scores correlated with participants' performance and learning progression, highlighting the importance of considering both objective and subjective measures in surgical training. CONCLUSIONS: The study underscores the importance of hand dominance in laparoscopic surgical training and suggests that personalized training protocols could enhance surgical precision, efficiency, and patient outcomes. By leveraging advanced analytical techniques, including Network Models and EMG data analysis, this research contributes to optimizing clinical training methodologies, potentially revolutionizing surgical education and improving patient care.

Excess dietary sugar impairs Drosophila adult stem cells via elevated reactive oxygen species-induced JNK signaling.

High-sugar diets (HSDs) often lead to obesity and type 2 diabetes, both metabolic syndromes associated with stem cell dysfunction. However, it is unclear whether excess dietary sugar affects stem cells. Here, we report that HSD impairs stem cell function in the intestine and ovaries of female Drosophila prior to the onset of insulin resistance, a hallmark of type 2 diabetes. Although 1 week of HSD leads to obesity, impaired oogenesis and altered lipid metabolism, insulin resistance does not occur. HSD increases glucose uptake by germline stem cells (GSCs) and triggers reactive oxygen species-induced JNK signaling, which reduces GSC proliferation. Removal of excess sugar from the diet reverses these HSD-induced phenomena. A similar phenomenon is found in intestinal stem cells (ISCs), except that HSD disrupts ISC maintenance and differentiation. Interestingly, tumor-like GSCs and ISCs are less responsive to HSD, which may be because of their dependence on glycolytic metabolism and high energy demand, respectively. This study suggests that excess dietary sugar induces oxidative stress and damages stem cells before insulin resistance develops, a mechanism that may also occur in higher organisms.

Loss of Activity-Induced Mitochondrial ATP Production Underlies the Synaptic Defects in a Drosophila Model of ALS.

Mutations in the gene encoding vesicle-associated membrane protein B (VAPB) cause a familial form of amyotrophic lateral sclerosis (ALS). Expression of an ALS-related variant of vapb (vapbP58S ) in Drosophila motor neurons results in morphologic changes at the larval neuromuscular junction (NMJ) characterized by the appearance of fewer, but larger, presynaptic boutons. Although diminished microtubule stability is known to underlie these morphologic changes, a mechanism for the loss of presynaptic microtubules has been lacking. By studying flies of both sexes, we demonstrate the suppression of vapbP58S -induced changes in NMJ morphology by either a loss of endoplasmic reticulum (ER) Ca2+ release channels or the inhibition Ca2+/calmodulin (CaM)-activated kinase II (CaMKII). These data suggest that decreased stability of presynaptic microtubules at vapbP58S NMJs results from hyperactivation of CaMKII because of elevated cytosolic [Ca2+]. We attribute the Ca2+ dyshomeostasis to delayed extrusion of cytosolic Ca2+ Suggesting that this defect in Ca2+ extrusion arose from an insufficient response to the bioenergetic demand of neural activity, depolarization-induced mitochondrial ATP production was diminished in vapbP58S neurons. These findings point to bioenergetic dysfunction as a potential cause for the synaptic defects in vapbP58S -expressing motor neurons.SIGNIFICANCE STATEMENT Whether the synchrony between the rates of ATP production and demand is lost in degenerating neurons remains poorly understood. We report that expression of a gene equivalent to an amyotrophic lateral sclerosis (ALS)-causing variant of vesicle-associated membrane protein B (VAPB) in fly neurons decouples mitochondrial ATP production from neuronal activity. Consequently, levels of ATP in mutant neurons are unable to keep up with the bioenergetic burden of neuronal activity. Reduced rate of Ca2+ extrusion, which could result from insufficient energy to power Ca2+ ATPases, results in the accumulation of residual Ca2+ in mutant neurons and leads to alterations in synaptic vesicle (SV) release and synapse development. These findings suggest that synaptic defects in a model of ALS arise from the loss of activity-induced ATP production.

Tumor Necrosis Factor-Alpha Exacerbates Viral Entry in SARS-CoV2-Infected iPSC-Derived Cardiomyocytes.

The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.

An Update on Mesoporous Silica Nanoparticle Applications in Nanomedicine.

The efficient and safe delivery of therapeutic drugs, proteins, and nucleic acids are essential for meaningful therapeutic benefits. The field of nanomedicine shows promising implications in the development of therapeutics by delivering diagnostic and therapeutic compounds. Nanomedicine development has led to significant advances in the design and engineering of nanocarrier systems with supra-molecular structures. Smart mesoporous silica nanoparticles (MSNs), with excellent biocompatibility, tunable physicochemical properties, and site-specific functionalization, offer efficient and high loading capacity as well as robust and targeted delivery of a variety of payloads in a controlled fashion. Such unique nanocarriers should have great potential for challenging biomedical applications, such as tissue engineering, bioimaging techniques, stem cell research, and cancer therapies. However, in vivo applications of these nanocarriers should be further validated before clinical translation. To this end, this review begins with a brief introduction of MSNs properties, targeted drug delivery, and controlled release with a particular emphasis on their most recent diagnostic and therapeutic applications.

Assessing Laparoscopic Surgical Skills Using Similarity Network Models: A Pilot Study.

Background: Medical devices are becoming more complex, and doctors need to learn quickly how to use new medical tools. However, it is challenging to objectively assess the fundamental laparoscopic surgical skill level and determine skill readiness for advancement. There is a lack of objective models to compare performance between medical trainees and experienced doctors. Methods: This article discusses the use of similarity network models for individual tasks and a combination of tasks to show the level of similarity between residents and medical students while performing each task and their overall laparoscopic surgical skill level using a medical device (eg laparoscopic instruments). When a medical student is connected to most residents, that student is competent to the next training level. Performance of sixteen participants (5 residents and 11 students) while performing 3 tasks in 3 different training schedules is used in this study. Results: The promising result shows the general positive progression of students over 4 training sessions. Our results also indicate that students with different training schedules have different performance levels. Students' progress in performing a task is quicker if the training sessions are held more closely compared to when the training sessions are far apart in time. Conclusions: This study provides a graph-based framework for evaluating new learners' performance on medical devices and their readiness for advancement. This similarity network method could be used to classify students' performance using similarity thresholds, facilitating decision-making related to training and progression through curricula.

WD40 protein Wuho controls germline homeostasis via TRIM-NHL tumor suppressor Mei-p26 in Drosophila.

WD40 proteins control many cellular processes via protein interactions. Drosophila Wuho (Wh, a WD40 protein) controls fertility, although the involved mechanisms are unclear. Here, we show that Wh promotion of Mei-p26 (a human TRIM32 ortholog) function maintains ovarian germ cell homeostasis. Wh and Mei-p26 are epistatically linked, with wh and mei-p26 mutants showing nearly identical phenotypes, including germline stem cell (GSC) loss, stem-cyst formation due to incomplete cytokinesis between GSCs and daughter cells, and overproliferation of GSC progeny. Mechanistically, Wh interacts with Mei-p26 in different cellular contexts to induce cell type-specific effects. In GSCs, Wh and Mei-p26 promote BMP stemness signaling for proper GSC division and maintenance. In GSC progeny, Wh and Mei-p26 silence nanos translation, downregulate a subset of microRNAs involved in germ cell differentiation and suppress ribosomal biogenesis via dMyc to limit germ cell mitosis. We also found that the human ortholog of Wh (WDR4) interacts with TRIM32 in human cells. Our results show that Wh is a regulator of Mei-p26 in Drosophila germ cells and suggest that the WD40-TRIM interaction may also control tissue homeostasis in other stem cell systems.